Further understanding of ethanol-related effects of the Pukinje neuron (PN), the sole output neuron of the cerebellar cortex, is essential due to the deleterious effects of alcohol on balance and motor coordination. Lengthy periods of ethanol consumption result in dendritic regression and dilatation of the dendritic smooth endoplasmic reticulum (SER) within the extensive dendritic arbor of PN. The SER within PN dendrites stores calcium ions, a function that may be upset by ethanol-related imbalances. Ethanol-related SER dilatation in PN dendrites, moreover, may predict and contribute to the ethanol-related dendritic regression that has been repeatedly observed in old rats. The first aim of this proposal is to characterize the development of SER dilation in PN dendrites at several time points during a lengthy period of ethanol consumption. This will relate the time when ethanol-related SER dilatation occurs to the time when PN dendritic regression has been reported. The second aim is to confirm and characterize ethanol-related SER dilatation in parallel fibers, the axons of granule neurons (GN). Parallel fibers provide a major synaptic input to the PN and a causal relationship may exist between ethanol-related SER dilatation in the presynaptic parallel fiber and the postsynaptic PN dendrite. SER dilatation is most probably a marker of neuronal imbalances that could severely impact on cerebellar output. One hundred and twenty old male F344 and 30 old female F3244 rats will be assigned to three treatment groups (50 rats/group). Treatment groups will include a chow control group, a pair-fed group, and an ethanol group. Ten males from each treatment group will be treated for a 5,10,20 or 40 week period, respectively. Length of treatment for the female rats will be determined by the time point at which SER dilatation reached significant levels in both PN dendrites and parallel fibers. Following treatment, rats will be euthanized, the cerebella removed and prepared for transmission electron microscopy (TEM). Image analysis of scanned TEM negative will be used to quantitative the maximum and minimum diameters of SER profiles in PN dendritic branches, branch points, and spines, and in parallel fibers.